9-Deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-4,4,5,5,13,14-hexadehydro-pgf1 compounds

ABSTRACT

The present invention relates to novel 9-deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-4,4,5,5,13,14-hexadehydro-PGF 1  compounds. These compounds are useful pharmacological agents, and are useful for the same purposes as the corresponding PGE-type compounds.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of Ser. No. 786,249, filed Apr. 11, 1977, now issued as U.S. Pat. No. 4,118,584.

The present invention relates to novel 9-deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-4,4,5,5,13,14-hexadehydro-PGF₁ compounds, the essential material constituting a disclosure of which is incorporated here by reference from U.S. Pat. No. 4,118,584. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## WHEREIN M₁ is ##STR2## wherein R₅ is hydrogen or methyl; WHEREIN L₁ is ##STR3## or a mixture of ##STR4## wherein R₃ and R₄ are hydrogen, mehtyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro;Wherein Z₉ is --C.tbd.C--CH₂ --(CH₂)_(g) --CH₂ or --CH₂ --C.tbd.C--(CH₂)_(g) --CH₂ -- wherein g is one, 2, or 3; wherein T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T's being the same or different, with the proviso that not more than two T's are other than alkyl; Wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl of one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation, and the 1,11- or 1,15-lactones thereof.
 2. A prostaglandin analog according to claim 1, wherein Z₉ is --CH₂ --C.tbd.C--(CH₂)_(g) --CH₂ --.
 3. A prostaglandin analog according to claim 2, wherein M₁ is ##STR5##
 4. 9-Deoxy-9-methylene-15-epi-4,4,5,5-tetradehydro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 3. 5. A prostaglandin analog according to claim 2, wherein M₁ is ##STR6##
 6. A prostaglandin analog according to claim 5, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 7. A prostaglandin analog according to claim 6, wherein g is
 3. 8. 9-Deoxy-9-methylene-2a,2b-dihomo-15-methyl-4,4,5,5-tetradehydro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 7. 9. 9-Deoxy-9-methylene-2a,2b-dihomo-4,4,5,5-tetradehydro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 7. 10. A prostaglandin analog according to claim 6, wherein g is one.
 11. A prostaglandin analog according to claim 10, wherein at least one of R₃ and R₄ is methyl.
 12. A prostaglandin analog according to claim 11, wherein R₃ and R₄ are both methyl.
 13. 9-Deoxy-9-methylene-16-methyl-4,4,5,5-tetradehydro-16-phenyl-18,19,20-trinor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 12. 14. A prostaglandin analog according to claim 10, wherein at least one of R₃ and R₄ is fluoro.
 15. A prostaglandin analog according to claim 14, where R₃ and R₄ are both fluoro.
 16. 9-Deoxy-9-methylene-16,16-difluoro-4,4,5,5-tetrahydro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 15. 17. A protaglandin analog according to claim 10, wherein R₃ and R₄ are both hydrogen.
 18. A prostaglandin analog according to claim 17, wherein R₅ is methyl.
 19. 9-Deoxy-9-methylene-15-methyl-4,4,5,5-tetradehydro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 18. 20. A prostaglandin analog according to claim 17, wherein R₅ is hydrogen.
 21. 9-Deoxy-9-methylene-4,4,5,5-tetradehydro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 20. 22. A prostaglandin analog according to claim 1, wherein Z₉ is --C.tbd.C--CH₂ --(CH₂)_(g) --CH₂.
 23. A prostaglandin analog according to claim 22, wherein M₁ is ##STR7##
 24. A prostaglandin analog according to claim 23, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 25. A prostaglandin analog according to claim 24, wherein g is
 3. 26. 9-Deoxy-9-methylene-2a,2b-dihomo-15-epi-15-methyl-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin analog according to claim
 25. 27. 9-Deoxy-9-methylene-2a,2b-dihomo-15-epi-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF.sub.2, a prostaglandin analog according to claim
 25. 28. A prostaglandin analog according to claim 24, wherein g is one.
 29. A prostaglandin analog according to claim 28, wherein at least one of R₃ and R₄ is methyl.
 30. 9-Deoxy-9-methylene-15-epi-16-methyl-16-phenyl-18,19,20-trinor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin analog according to claim
 29. 31. A prostaglandin analog according to claim 28, wherein at least one of R₃ and R₄ is fluoro.
 32. 9-Deoxy-9-methylene-15-epi-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF.sub.2, a prostaglandin analog according to claim
 31. 33. A prostaglandin analog according to claim 28, wherein R₃ and R₄ are both hydrogen.
 34. 9-Deoxy-9-methylene-15-epi-16-methyl-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF.sub.2, a prostaglandin analog according to claim
 33. 35. A prostaglandin analog according to claim 23, wherein M₁ is ##STR8##
 36. A prostaglandin analog according to claim 35, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 37. A prostaglandin analog according to claim 36, whrein g is
 3. 38. A prostaglandin analog according to claim 37, wherein at least one of R₃ and R₄ is methyl.
 39. 9-Deoxy-9-methylene-2a,2b-dihomo-16-methyl-16-phenyl-18,19,20-trinor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin analog according to claim
 38. 40. A prostaglandin analog according to claim 37, wherein at least one of R₃ and R₄ is fluoro.
 41. 9-Deoxy-9-methylene-2a,2b-dihomo-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin analog according to claim
 40. 42. A prostaglandin analog according to claim 37, wherein R₃ and R₄ are both hydrogen.
 43. 9-Dexoy-9-methylene-2a,2b-dihomo-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin analog according to claim
 42. 44. A prostaglandin analog according to claim 36, wherein g is one.
 45. A prostaglandin analog according to claim 44, wherein at least one of R₃ and R₄ is methyl.
 46. A prostaglandin analog according to claim 45, wherein R₃ and R₄ are both methyl.
 47. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-5,6,13,14-tetradehydro-PGF₂, tris-(hydromethyl)aminomethane salt, a prostaglandin analog according to claim
 46. 48. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-13,14-dihydro-5,6-didehydro-PGF₂, methyl ester, a prostaglandin analog according to claim
 46. 49. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-5,6,13,14-tetradehydro-PGF₂, methyl ester, a prostaglandin analog according to claim
 46. 50. A prostaglandin analog according to claim 44, wherein at least one of R₃ and R₄ is fluoro.
 51. A prostaglandin analog according to claim 50, wherein R₃ and R₄ are both fluoro.
 52. A prostaglandin analog according to claim 51, wherein R₅ is methyl.
 53. 9-Deoxy-9-methylene-15-methyl-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin analog according to claim
 52. 54. A prostaglandin analog according to claim 51, wherein R₅ is hydrogen.
 55. 9-Deoxy-9-methylene-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin analog according to claim
 54. 56. A prostaglandin analog according to claim 44, wherein R₃ and R₄ are both hydrogen.
 57. A prostaglandin analog according to claim 56, wherein R₅ is methyl.
 58. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, tris-(hydroxymethyl)aminomethane salt, a prostaglandin analog according to claim
 57. 59. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, methyl ester, a prostaglandin analog according to claim
 57. 60. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin analog according to claim
 57. 61. A prostaglandin analog according to claim 56, wherein R₅ is hydrogen.
 62. 9-Deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF.sub.2, methyl ester, a prostaglandin analog according to claim
 61. 63. 9-Deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-5,6,13,14-tetradehydro-PGF₂, a prostaglandin according to claim
 61. 